Abstract
We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH) and the protective effects mediated by angiotensin 1-7 [Ang(1-7)]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g) to normoxia control, CIH, Ang(1-7)-treated normoxia, and Ang(1-7)-treated CIH groups. Systolic blood pressure (SBP) was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA) was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7) induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7) treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7) treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7) might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.
Highlights
Obstructive sleep apnea (OSA) is a chronic disease that influences several systems in vivo
We focused on the effects of Ang[1,2,3,4,5,6,7] treatment at various levels as indicated by oxidative stress markers, structural modifications, inflammation markers, and renal apoptosis
Systolic blood pressure (SBP) As observed by indirect determination, chronic intermittent hypoxia (CIH) rats displayed a significant increase in SBP compared with the Norm and NormAng groups from the end of the second week (14 days: CIH vs Norm vs NormAng: 125.5±7.4 vs 100.8± 5.3 vs 100.0±6.1 mmHg; CIH vs Norm: Po0.0001, CIH vs CIHAng: P=0.001)
Summary
Obstructive sleep apnea (OSA) is a chronic disease that influences several systems in vivo. It is characterized by the obstruction of the upper airways with repetitive pauses in breathing during sleep (despite efforts to breathe) as well as by daytime sleepiness [1]. Fletcher [5] has emphasized the causal link between chronic intermittent hypoxia (CIH) and increased arterial pressure. Patients with severe OSA exhibit a high prevalence of chronic kidney disease (CKD) and it has further been found to accelerate the loss of kidney function. Animals exposed to intermittent hypoxia suffer histopathological renal damage [7]. The underlying mechanism of this association remains unclear despite the progress made by many studies in understanding OSA and renal injury
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